It is the general aim of this research to utilize a well defined central autonomic system in the analysis of the mechanisms by which adrenergic drugs influence the central nervous system (CNS). The central structures controlling or modulating parasympathetic tone to the iris comprise the only CNS autonomic system where one can study the direct effects of drugs on specific, well defined preganglionic neurons by means of microelectrode techniques. In addition, this system has equally well defined excitatory and inhibitory inputs which can be controlled experimentally. The initial objective of this research will be to systematically determine the mechanism and site of action of clonidine on this model system and to study the interactions between clonidine and other drugs such as yohimbine and the tricyclic antidepressants in order to further clarify our understanding of central adrenergic mechanisms. Other experiments will be conducted which may be useful in the interpretation of the action of clonidine as well as in the elucidation of the possible endogenous neurotransmitter mechanisms of this system. The methodology employed will include peripheral nerve and single neuron recordings, peripheral and CNS stimulation techniques, catecholamine determinations, and lesion and ablation procedures.